Abstract

The specific aims are to: 1) Assess the role of the gp39/CD40 interaction in the induction of intrathymic clonal deletion by superantigens in normal mice or by peptide antigens in TCR transgenic mice. Attempts will be made to identify the critical CD40+ cell in this system. 2) Assess the role of the gp39/CD40 interaction in the induction of peripheral tolerance by B-cells. Studies will be aimed at determining the cellular basis for this phenomenon using conventional and TCR transgenic mice. 3) Determine how blockage of the gp39/CD40 interaction prevents EAE. Attempts will be made to determine if macrophage functions are affected or if T-cell tolerance is induced.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI037075-04
Application #
2672417
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1995-09-01
Project End
1999-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Dartmouth College
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755

  Publications

Becher, B; Durell, B G; Miga, A V et al. (2001) The clinical course of experimental autoimmune encephalomyelitis and inflammation is controlled by the expression of CD40 within the central nervous system. J Exp Med 193:967-74
Miga, A J; Masters, S R; Durell, B G et al. (2001) Dendritic cell longevity and T cell persistence is controlled by CD154-CD40 interactions. Eur J Immunol 31:959-65
Howard, L M; Miga, A J; Vanderlugt, C L et al. (1999) Mechanisms of immunotherapeutic intervention by anti-CD40L (CD154) antibody in an animal model of multiple sclerosis. J Clin Invest 103:281-90
Buhlmann, J E; Gonzalez, M; Ginther, B et al. (1999) Cutting edge: sustained expansion of CD8+ T cells requires CD154 expression by Th cells in acute graft versus host disease. J Immunol 162:4373-6
Gonzalez, M; Mackay, F; Browning, J L et al. (1998) The sequential role of lymphotoxin and B cells in the development of splenic follicles. J Exp Med 187:997-1007
Mackey, M F; Gunn, J R; Maliszewsky, C et al. (1998) Dendritic cells require maturation via CD40 to generate protective antitumor immunity. J Immunol 161:2094-8
Mackey, M F; Gunn, J R; Ting, P P et al. (1997) Protective immunity induced by tumor vaccines requires interaction between CD40 and its ligand, CD154. Cancer Res 57:2569-74